The overall goal of this work is to develop functional magnetic resonance and optical imaging techniques that allow non-invasive assessment of brain and heart function. A secondary goal is to combine moelcular genetics with non-invasive imaging to understand cellular energetics and the role of the enzyme creatine kinase. Over the past year we have spent significant energy establishing the new Laboratory of Functional and Molecular Imaging at NINDS. Major renovations to the In Vivo NMR Center are nearing completion to significantly extend animal imaging rsources at NIH. An 11.7 Tesla MRI for animals has recently been delivered and should be fully functional in the fall. This very high field MRI should allow extension of MRI spatial resolution and sensitivity of fucntional MRI. In addition, space and equipment for the new Mouse Imaging Facility are being established. This facility will become operational in the fall and new equipment including high frequency ultra-sound, CT, and MRI fully functioning by Summer, 2001. Design has been completed on another addition to the In Vivo NMR Center to house a NIMH/NINDS 3T human MRI and a NINDS/NIMH 7T MRI. The goal is to complete renovation and take delivery of these systems by summer 2001.Scientifically, progress has been made on three fronts. We have extended MRI techniques to measure regional blood flow to measure vascular transit times and arterial and venous volumes. Originally developed by us, these MRI regional blood flow techniques are becoming standard tools for assessment of the normal and diseased brain. Our recent work should extend the applicability and sensitivity of these techniques. In addition, we have continued to develop the use of manganese ion as a functional MRI contrast agent to assess calcium influx. Recent work demonstrates that we can detect activation of specific areas of the olfactory bulb due to specific odors in mice and track the connections of these olfatory bulb regions to the primary olfactory cortex using MRI. In the heart, we have demonstrated that manganese accumulation can be detected by MRI and is proportional to calcium influx rate during different inotropic states. Finally, we have an exciting finding that the mitochondrial isoform of creatine kinase protects transgenic mouse liver and mice from septic shock. This combined with previous results that the mitochondiral isoform of creatine kinase can inhibit liver regeneration clearly indicates a role for creatine kinase in cell death and cell division. Recently developed two-dimensional gel electrophoresis techniques will allow us to compare protein changes that occur due to creatine kinase expression.